Wednesday, 25 February 2015

 (General principles of microbial concepts)

Microorganisms (Latin micro = small) are living beings so small (< 40 µm or 0.04 mm) that they are not visible by the naked eye. Microorganisms related to human health include certain bacteria, viruses, fungi and parasites.

Types of Microorganisms:

Microorganisms can be, according to their characteristics, divided into several groups:
  • bacteria, viruses, certain fungi and parasites
  • pathogenic (capable of causing disease), non-pathogenic, and opportunistic (causing disease when they have an opportunity, like in people with low immune system)
  • acellular (without cell, like viruses), unicellular (bacteria, yeasts and certain parasites), or multi-cellular (molds)

 1. Bacteria
Bacteria are unicellular organisms, about few microns in size (1 micron (µm) = 1/1,000 of a millimetre), consisting of DNA, cytoplasm, structures needed for metabolism and reproduction, cell membrane, cell wall and capsule .Certain bacteria use flagella, tail-like appendages, to propel themselves.

  Bacterial structure

Bacteria multiply asexually by dividing into two daughter cells
Bacteria can be divided into several groups:
  • Spheres or cocci (like Staphylococcus aureus), rods or bacilli (like Lactobacillus acidophilus), spirals or spirochetes (like Treponema pallidum); bacterial shape can help in their recognizing under the microscope
  • Aerobic bacteria, like Mycobacterium tuberculosis, need oxygen to thrive, while  anaerobic, like Clostsridium difficile, do not. Facultative anaerobic bacteria, like Pseudomonas aureginosa, can live in aerobic and anaerobic environment.
  • Gram positive (G+) bacteria, like Streptococcus, and Gram negative (G-) bacteria, like Klebsiella
  • Pathogenic and non-pathogenic bacteria

Certain bacteria can form endospores, a kind of encapsulated bunkers within a bacteria that enable vital parts of bacteria to survive in harsh conditions, like freezing or boiling water, dessication, lack of nutrients, etc. Some bacteria can survive weeks, and some millions of years in this form.
In the human body, bacteria usually cause localized infections, like pneumonia or skin infections. Bacterial infections can be diagnosed by growing a bacterial culture from a sample of infected body fluid (e.g. urine, blood), stool, discharge (e.g. sputum) or tissue (e.g. mucosal layer of the stomach). Most of bacterial infections can be successfully treated by anti-bacterial drugs – antibiotics.
Examples of bacteria pathogenic for a human are:
  • Staphylococcus aureus, causing skin infections, pneumonia, and infection of the heart valves, etc.
  • Streptococcus pyogenes, causing “strep throat”, cellulitis, etc.
  • Neisseria gonorrheae, causing gonorrhea
  • Salmonella, causing diarrhea in food poisoning
  • Helicobacter pylori, causing chronic gastritis
  • Mycoplasma, causing atypical pneumonia

Examples of non-pathogenic bacteria:
  • Staphylococcus epidermidis, a part of normal skin flora
  • Lactobacillus acidophilus, a part of normal intestinal flora
Examples of opportunistic bacteria:
  • Certain intestinal bacteria, like Escherichia coli and Enterobacter live in the human intestine without causing any symptoms, but in a person with lowered immune system they may overgrow and cause a bowel infection.

2. Viruses

Viruses are simple microorganisms, containing only DNA or RNA molecule and capsule. They cannot survive outside the host for long periods, so they are mainly transmitted by blood-to-blood or stool-to-mouth route. In the human body, they have to invade the cells to multiply

Virus cycle: entry of herpes simplex virus (HSV) into the cell (on the left), multiplying within the cell and release (right) from the cell 

Viruses usually cause systemic infections, affecting the whole body. Examples of viruses, pathogenic for a human:
  • Rhinovirus, causing common cold
  • Influenzavirus, causing flu, bird flu, swine flu
  • Herpes simplex virus causing herpes labialis (cold sore) or herpes genitalis
  • HIV, causing AIDS
  • Ebolavirus, causing hemorrhagic fever
Viruses can be diagnosed by finding specific antibodies in the sample of blood (serologic tests). Vaccination against several virus infections is possible; only few viral infections can be treated by anti-viral medications, though.

3. Fungi

Fungi are widely present in the environment and also on the human skin, gut and vagina.
Fungi are subdivided on the basis of their life cycles, the presence or structure of their fruiting body and the arrangement of and type of spores (reproductive or distributional cells) they produce.
The three major groups of fungi are:
·         multicellular filamentous moulds
·         macroscopic filamentous fungi that form large  fruiting bodies. Sometimes the group is referred  to as ‘mushrooms’, but the mushroom is just the part of the fungus we see above ground which is also known as the fruiting body.
·         single celled microscopic yeasts

4. Parasites

Human intestinal parasites are either one-cell organisms or intestinal worms that live in the small or large intestine and use the stool or blood from intestinal wall as a source of food.

One-cell organisms, like Giardia lamblia, also called Giardia duodenale 
 1),Cryptosporidium (crypto) and Cyclospora, utilize nutrients from the stool. They belong to a living kingdom Protozoa (Gk. protos = first; zoa = animals). They may cause inflammation of thesmall intestine thus hampering absorption of nutrients. Entamoeba hystolytica lives predominantly in the colon.

Intestinal Worms (Helminths):

Intestinal worms (helminths), like roundworms (hookworms), whipworms,  Ascaris andTrichinella), tapeworms and flukes, are few millimeters to several meters in size, they eat the bowel content or suck the blood from the intestinal wall and can cause about the same symptoms as one-cell parasites.


Beneficial Microorganisms

Microorganisms, like certain bacteria and yeasts, living on the human skin or in the nose, mouth, throat, small and large intestine and vagina, are part of the normal human flora; they prevent overgrowth of harmful microorganisms. Some of these microbes, when overgrow, may become pathogenic, though.

Harmful or Pathogenic Microorganisms

Pathogenic means capable of causing disease. An actual harmful effect of a microbe to the body depends on:

  • Microbial virulence - a relative ability of a microbe to cause a disease; for example, a certain, highly virulent subtype of influenza virus may cause a bird flu, which is deadly in a high percent, while “usual” influenza virus is not.
  • Invasion through the body’s barriers; staph bacteria might not cause any harm to a person with an intact skin, but can cause a severe infection of a skin wound.
  • Amount of microbes; eating few bites of food contaminated with staph bacteria may go unnoticed, while eating the whole portion of the same food may cause a severe food poisoning.
  • Body’s defense (immune) system; patients with a weak immune system, like those receiving corticosteroids, often get oral thrush (candida infection of the mouth), while otherwise healthy people do not.

Tuesday, 17 February 2015

 Physiology of Nervous system

The nervous system has two major parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The central system is the primary control center for the body and is composed of the brain and spinal cord. The peripheral system consists of a network of nerves that connects the rest of the body to the CNS.
The two systems work together to collect information from inside the body and from the environment outside it. The systems process the collected information and then dispatch instructions to the rest of the body, making it respond.
In most cases, the brain is the destination for information gathered by the rest of the nervous system. Once data arrives, the brain sorts and files it before sending out any necessary commands.
The brain is divided into many different sections, including the cerebrum and brain stem. These parts handle pieces of the brain’s overall workload, including storing and retrieving memory and making body movements smooth.
Although the brain is the control center, its job would not be possible without the spinal cord, which is the major conduit for information traveling between brain and body.
Peripheral system nerves branch from either the brain stem or the spinal cord. Each nerve is connected to a particular area of the torso or limbs and is responsible for communication to and from those regions.
The PNS can also be divided into smaller pieces: the somatic and autonomic systems. The somatic involves parts of the body a person can command at will, and the autonomic helps run involuntary functions such as pumping blood.
Information conveyed through the nervous system moves along networks of cells called neurons. These neurons can only send information one way. Those transmitting to the brain are sensory neurons; those that transmit from the brain are known as motor neurons.

The nervous system can suffer from a number of afflictions, including cancer. Other problems include multiple sclerosis, in which damaged nerves prevent signals from traveling along them, and meningitis, which causes an inflammation of the membranes surrounding the brain and spinal cord.

Monday, 9 February 2015

Inter-cellular signaling by cytokines between B-cells, T- cells, and effector cells

B cell activation

A key part of the immune system is the production of immunoglobulins (antibodies) by B cells to bind and inactivate specific foreign antigens. The body produces B cells with a wide range of antigen specificities in the immunoglobulin B cell receptor, one antigen specificity per cell. When the B cell receptor immunoglobulin binds antigen, that cell is activated to proliferate and create plasma cells secreting immunoglobulins to bind that specific antigen. B cell activation also creates memory cells with the same antigen specificity that do not actively secrete immunoglobulin but provide for rapid future immune responses to the same antigen.
B cells are not activated by antigen on their own, but require interaction with helper CD4+ T cells to become activated and proliferate. The B cell first expresses immunoglobulin on the cell surface as the B cell receptor. If the B cell receptor immunoglobulin binds specific antigen, then the cell internalizes the antigen and presents it to T cells in MHC II, where it is recognized by the T cell receptor. In addition to the interaction between the T cell receptor and the B cell MHC-antigen, T cell interaction with the B cell involves additional positive and negative regulatory signals. CD40 interaction with CD40L and CD28 interaction with CD80 provide positive costimulatory signals that stimulate B cell activation and proliferation. T cell receptor activation induces expression of molecules like the CD40 ligand that modulate the B cell-T cell interaction. The CD40-CD40L interaction induces cytokine production and expression of other genes and alters the fate of the B cell involved in the interaction. If the interaction between CD40 and CD40L is prolonged, the B cell can be induced to become a memory cell rather than a plasma cell. Fas ligand binding to Fas between B and T cells may negatively modulate B cell activation, inducing apoptosis that limits B cell proliferation and activation. Cytokines like IL-2, IL-4 and IL-10 also play an important role in B cell activation.

T cell activation

T helper cells play an essential role coordinating the activities of other parts of the immune system, including B cells, cytotoxic T cells, macrophages and other cells. The crucial nature of helper T cells in the normal immune response is demonstrated by the severe immune deficiency associated with the HIV-induced helper T cell depletion. To communicate with other cells, helper T cells express a range of cell surface molecules, a few of which are illustrated in this figure. Like all T cells, helper T cells express T cell receptors complexed with the CD3 proteins that are responsible for the recognition and response of the cell to specific antigens (see “T Cell Receptor Signaling Pathway”). CD4 is commonly used as a marker for helper T cells, in contrast to cytotoxic T cells, which express CD8. CD4 is used by HIV to gain cell entry, as well as the CCR5 chemokine receptor. Thy1 provides a more general cell surface antigen used to identify both T helper and cytotoxic T cells. CD28 provides a costimulatory signal in association with the activation of the T cell receptor complex by an antigen presenting cell that is required for the T cell to become activated (see “The Co-Stimulatory Signal during T-cell Activation” pathway). Adhesion molecules on the surface of T cells assist in their interaction with other cells. LFA-1 binds to its ligand ICAM-1 in a variety of cells and T cells themselves also express ICAM-1. The CD45 protein tyrosine phosphatase dephosphorylates factors in the pathways involved in B cells and T cells activation. Although CD45 is required for T cell receptor activation, exclusion of CD45 from the local membrane region near the T cell receptor appears important for efficient T cell activation. Helper T cells can be subdivided further into Th1 and Th2 cells, distinguished by their response to different antigens, differing cytokine expression and expression of different chemokine receptors (see “Selective expression of chemokine receptors during T-cell polarization”) CD2 is required for efficient helper T cell maturation and stimulates their differentiation, but does not select for a specific increase in Th1 or Th2 populations of cells.

Wednesday, 4 February 2015

The basic structure of Immunoglobulins

Increases in:
a) Chronic granulomatous infections
b) Infections of all types
c) Hyperimmunization
d) Liver disease
e) Malnutrition (severe)
f) Dysproteinemia
g) Disease associated with hypersensitivity granulomas, dermatologic disorders, and IgG myeloma
h) Rheumatoid arthritis
Decreases in:
a) Agammaglobulinemia
b) Lymphoid aplasia
c) Selective IgG, IgA deficiency
d) IgA myeloma
e) Bence Jones proteinemia
f) Chronic lymphoblastic leukemia

1. Increases (in adults) in:
a) Waldenström's macroglobulinemia
b) Trypanosomiasis
c) Actinomycosis
d) Carrión's disease (bartonellosis)
e) Malaria
f) Infectious mononucleosis
g) Lupus erythematosus
h) Rheumatoid arthritis
I) Dysgammaglobulinemia (certain cases)

Note: In the newborn, a level of IgM above 20 ng./dl is an indication of in uterostimulation of the immune system and stimulation by the rubella virus, the cytomegalovirus, syphilis, or toxoplasmosis.

2. Decreases in:
a) Agammaglobulinemia
b) Lymphoproliferative disorders (certain cases)
c) Lymphoid aplasia
d) IgG and IgA myeloma
e) Dysgammaglobulinemia
f) Chronic lymphoblastic leukemia

1. Increases in:
a) Wiskott-Aldrich syndrome
b) Cirrhosis of the liver (most cases)
c) Certain stages of collagen and other autoimmune disorders such as rheumatoid arthritis and lupus erythematosus
d) Chronic infections not based on immunologic deficiencies
e) IgA myeloma
2. Decreases in:
a) Hereditary ataxia telangiectasia
b) Immunologic deficiency states (e.g., dysgammaglobulinemia, congenital and acquired agammaglobulinemia, and hypogammaglobulinemia)
c) Malabsorption syndromes
d) Lymphoid aplasia
e) IgG myeloma
f) Acute lymphoblastic leukemia
g) Chronic lymphoblastic leukemia

1. Increases in:
a) Chronic infections
b) IgD myelomas

1. Increases in:
a) Atopic skin diseases such as eczema
b) Hay fever
c) Asthma
d) Anaphylactic shock
e) IgE-myeloma
2. Decreases in:
a) Congenital agammaglobulinemia
b) Hypogammaglobulinemia due to faulty metabolism or synthesis of immunoglobulins