Causes For Throat Infections And Irritations Biology Essay

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Streptococcal throat infections are very common in the winter season. These infections are caused by a Gram+ve bacteria i.e Streptococcus pyogenes. Streptococcus pyogenes is a beta-hemolytic bacterium that belongs to Lancefield serogroup A. This is a capsulated bacterium. These bacteria often colonized in the upper respiratory tract of humans by overcoming the host defiance mechanisms. The bacteria cause mainly skin and respiratory tract disorders. Pyogenes are complex and chemically diverse. The antigenic components of the cell are the virulence factors. The extracellular components responsible for the disease process include invasins and exotoxins. The outermost capsule is composed of hyaluronic acid, which has a chemical structure resembling host connective tissue, allowing the bacterium to escape recognition by the host as an offending agent. The carbohydrate capsules protect the bacteria from the phagocytic effect of the body. The bacteria get in to the host body through the air, which is taken both by nose and mouth. The bacteria are aerobic in nature that is why it always gets colonized at the sites where it gets sufficient oxygen.

Review of literature:

Group A bacteria are the parasites in human having 90 serotypes. It is estimated that 5-15% of normal individual contains streptococcus in their throats and the respiratory tract without signs of disease (asymptomatic). When it successfully defeats the host's immune system gets multiplies and causes acute infections [1]. Acute streptococcal infections may occur as pharyngitis or strep throat. Patient may also develop post streptococcal disease such as acute rheumatic fever and glomerulonephritis with is more like an auto immune disease or antibody interaction of the body. Streptococcus pyogenes produces a wide array of virulent factors and a range of diseases. Virulency of Group A streptococcus includes M protein: virulent protein and lipolithic acids for adherence [4]. Hyaluronic acid capsules: as an immune disguiser and protecting it from Phagocytosis of the body, Invacins: such as streptokinase, streptodornase, hyalurinodase and Streptolysin, which causes cytolysis in host cell, Endotoxins: such as pyrogenin toxin which causes rashes of scarlet fever and systemic toxic shock syndrome [1]. Streptococcus pyogenes owes its major success as a pathogen to its ability to colonize and rapidly multiply, spread in its host while evading phagocytosis and confusing the immune system. Small self replicating double standard DNA (plasmid) is the genetic material of streptococcus pyogenes. Acute diseases associated with Streptococcus pyogenes occur chiefly in the respiratory tract, bloodstream, or the skin (pyoderma) [1].Infection (S. pyogenes is the leading cause of uncomplicated bacterial pharyngitis and tonsillitis commonly referred to a strep throat. S. pyogenes infections can also result in sinusitis, otitis, mastoiditis, pneumonia, joint or bone infections, necrotizing fasciitis and myositis, meningitis or endocarditis [1]. Signs of a Strep Throat are fever above 101° F or 38 °C, chills, throat pain, trouble swallowing, neck swelling, trouble breathing, body aches, loss of appetite, nausea or vomiting, abdominal pain. Pharyngitis is also accompanied by other symptoms such as red throat, runny or stuffy nose, dry cough, hoarseness, redness of eyes, joint pain and muscle ache, skin rashes and swollen lymph node in the neck [1]. Children may have diarrhea, sometimes lower WBC and lymphocytic shift, less tonsillar exudates (an exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation) [3]. The bacterium uses the TGFβ1 gene of human host for repeated multiplication. TGF-β1 is the positive regulator of the integrin signal pathway by up-regulating integrin-linked kinase, phosphoinositide 3-kinase (PI3K), paxillin, and focal adhesion kinase (FAK). Actually TGFβ1 is the gene which encodes for 390 amino acids, signal peptides, and 29 receptors.


The key mechanism of streptococcal infections is as follows:

First the microbe enters body through the air we are taking by breath. The microorganism is then entered in the tonsil cells by phagocytosis, which is a cell eating process. S.pyogenes secretes a vast range of enzyme which infects the host tissue. Hyaluronidase degrades hyaluronic acid, a compound that cements cells together in much mammalian system. This help in degradation of hyaluronic acid which cements cell together in human host. Secretion of DNAse, RNAse and protease also aid the microbe. It contains M protein or Fn binding protein which is the virulent factor of pyogenes. As shown in the figure-1 the fibronectin binding protein is then binds with the integrin of host with the help of RGD motif of bacteria. The integrin are the group of proteins which forms the extracellular matrix of cell (Fibronectin, collagens, laminin etc) [4]. When the bacteria get integrated with the proteins the tonsils get infected. The infected tonsil are the main source of TGFβ1 (transforming growth factor) genes are activated. When the gene is activated it encodes for a receptor α5β1 receptor in the cell [3]. The receptor actively binds with the M protein of the bacteria in a lock and key fashion. This binding helps the bacteria to multiply and increase in size.

Figure.1 the mechanism of streptococcus action inside body.RGD is the bacterial motif.

After multiplying millions of bacteria are form and they produce toxin called HEMOLYSINS which is labile, cause lysis of WBCs, platelets, tissue cells. This toxin is the factor which causes apoptosis host cell. Due to the accumulation of cell debris and broken WBCs are the cause of swelling in host tissues. HYALURONIDASE (spreading factor), Lysis of hyaluronic acid- spread of infection in surrounding art of the infected cells. Mef (A) gene codes for a group of protein which gives the bacteria resistance to a series of microlides (antibiotics). This gene stimulates the expression of Fn protein and M1 protein of the bacteria which gives it pathogenic nature [3].

After binding to the cell:

The initial invasion causes the secretion of bradykinin and other chemokinins from the damaged cells. The bradykinin can initiate the inflammation process. Bradykinin binds with the receptor of the blood vessel cell nearby capillaries, which creates gaps in the blood vessels. Microbial product and chemokinins leaks in the blood stream surrounding. The above process may attract the attention of phagocytes and they begin to migrate towards the area and attack the invasion of bacterial pathogens. The neutrophils attacks bacteria and they get clumped in to the bacteria producing pus. The pus run down to the back of the throat and which shows a white or yellow pus accumulation. Inside the lymph nodes processed antigens lying in the cleft of MHCII molecule and presented to a series of T-helper cells. Successful interaction between TCR of a TH2 cells and IL-1, IL-6 are formed from the microphages. IL-1 interacts with hypothalamus and increase body temperature. The increased temperature will activate the t-cell to work more quickly.

Conclusion: From the above studies it is proved that the bacteria Streptococcus pyogenes is a very pathogenic bacterium. It is resistant to a group of antibiotics. The capsulated bacteria take the help of host cell mechanism for the multiplication. It causes strep throat, rheumatic fever, many upper respiratory infections such as Sinusitis, Epiglottitis, and Laryngitis in human host. The disease are many time fetal. It is actually an aerobic bacteria therefore it infects and colonizes only in that area where they get sufficient 0xigen. Throat and skin are therefore the main sites of infection.




3. 10/2005. Developed through a partnership of The Ohio State University Medical Center, Mount Carmel Health and OhioHealth, Columbus, Ohio.North Dakota Department of Health, Rev, September2005.4. John J. Mekalanos Beinan Wang, Shaoying Li, Peter J. Southern, and Cleary P. December 21, 2005. Streptococcal modulation of cellular invasion via TGF-β1 signaling.vol. 103, pp.2380-2385.Harvard Medical School.



Whooping cough by the bacterium Bordetella pertussis. This bacterium is very small Gram negative aerobic coccobacillus that appears in pairs or singly. This bacterium is nutritionally fastidious and are usually cultivated on rich media which is supplemented with blood. Whooping cough is a contagious disease. This disease is characterized by whoop sound made from the inspiration sound made by air in time of cough. This is a fetal disease and kills 300,000 persons annually. Signs are fever and sore throat. Some time due to frequent cough vomiting occurs and which leads to malnutrition in children. Sometimes runny nose, sneezing, low-grade fever, mild occasional cough, similar to common cold. However, before the diagnosis of whooping cough the bacteria have already done much damage. After Cell-bound pertussis toxin and other toxins have broken down the cilia and wounds are exposed, the body then wants to rid of the drainage from the wounds. At first slightly productive cough, but as the bacteria continue to colonize there is more and more drainage. The increased need to expel the drainage results in violent, uncontrollable coughing, with a distinct gasp of air following. This gasp of air is described as a whooping noise, thus we get the term whooping cough.

Review of literature

Bordetella pertussis colonizes at cilia of the mammalian respiratory epithelium. Sometimes they can be colonized in the alveolar macrophage. The bacteria are a pathogen for human and in higher primates. The disease is very much fatal in case of the infants. It has two stages: In the 1st stage, colonization in the upper respiratory tract with fever, coughing. This increases with intensity over about 10 days. During this stage the bacteria can be recovered in large no. from the pharyngeal culture. Sometime the mechanism involves the "filamentous hemagglutinin" (FHA), which is a structure in the bacterial surfaces, contains a cell-bound pertussis toxin (PTx). This short range effect of soluble toxins plays important role as well in the invasion during the colonization stage. Filamentous hemagglutinin is a large (220kDa) protein that forms filamentous structure on the cell surface. FHA binds to galactose residues on a sulfated glycolipid called sulfatide which is very common on the surface of ciliated cells. Mutations in the FHA structural gene reduce the ability of the organism to colonize, and antibodies against FHA provide protection against infection. However, that FHA is the only adhesin involved in colonization. Another toxins (PTx) involves in adherence to the epithelium of trachea. Pertussis toxin is a 105 kDa protein which composed of six subunits S1, S2, S3, S4, and S5 [1]. The toxin is both secreted into the extracellular fluid and got bound in to the cell. Some components of the cell-bound toxin (S2 and S3) function as adhesins, and appear to bind the bacteria to host cells. S2 and S3 utilize different receptors on host cells. S2 binds specifically to a glycolipid called lactosylceramide, which is found primarily on the ciliated epithelial cells. S3 binds to a glycoprotein found mainly on phagocytic cells. The S1 subunit of pertussis toxin is the A component with ADP ribosylating activity, and the function of S2 and S3 is presumed to be involved in binding the intact (extracellular) toxin to its target cell surface [5]. Antibodies against PTx components prevent colonization of ciliated cells by the bacteria and provide effective protection against infection. Thus, pertussis toxin is clearly an important virulence factor in the initial colonization stage of the infection. Since the S3 subunit of pertussis toxin is able to bind to the surface of phagocytes, and since FHA will attach to integrin CR3 on phagocyte surfaces (the receptor for complement C3b), it has been seen that the bacterium might bind preferentially to phagocytes in order to facilitate its own engulfment. The role of such self-initiated phagocytosis is not clear. This microbe taken up by this abnormal route may avoid stimulating the oxidative burst that normally accompanies phagocytic uptake of bacterial. The cells are then opsonized by antibodies or complement C3b [6].

Once inside of cells the bacteria might utilize other toxins (i.e. adenylate cyclase toxin) to compromise the bactericidal activities of phagocytes. The bacteria use this mechanism for invading the host. If B. pertussis is an intracellular parasite it would explain why immunity to pertussis correlates better with the presence of specific cytotoxic T cells than it does with the presence of antibodies to bacterial products [4]. B. pertussis produces at least two other types of adhesins, fimbriae and a nonfimbrial surface protein called pertactin.

The second stage called as the toxemic stage of pertussis follows relative nonspecific symptoms of the colonization stage. It causes prolong and paroxysmal coughing which end with a sound of whoop. During this stage the antimicrobial drug can effect on the progress of the disease. It secretes its own invasive adenylate cyclase that enters mammalian cells. This toxin acts locally to reduce phagocytic activities, probably help the organism initiate infection [4].

The adenylate cyclase is a hemolysin because it lyses blood cells, which is responsible for the haemolytic zone around the colonies of B.pertussis growing on blood sugar. It enters the erythrocyte membrane which causes hymolysis.

The adenylate cyclase toxin is only activated in the presence of calmoduin (calcium binding protein) which is a eukaryotia regulatory molecule (adenylate cyclase regulator). It produces a highly lethal toxin causing inflammation and local necrosis in the presence of the bacteria. It produces the pertussis toxin i.e tracheal cytotoxin which is toxic for ciliated respiratory epithelium and which will stop the cells from beating. This is a peptidoglycan fragment which appears in the extracellular fluid at the growing zone of bacteria.

One more factor that is tracheal colonization factor (TCF) which structure is similar to pertactin. It helps to colonizing of the microbe in trachea.

Pertussis toxin, an AB5 exotoxin is an important virulent factor of Bordetella pertussis. PT is composed of one A subunit (S1) and five B subunits (S2, S3, 2 subunits of S4, and S5) [8] .S1 ADP-ribosylates the alpha-subunits of some membrane-associated heterotrimeric G protein in mammalian cells. This may disrupt signals transduction events. The B oligomer mediated binding of pertussis toxin to the surface cells via a receptor which is glucoconjugated [9]. Increased intracellular cAMP affects normal biological signaling. The toxin causes several systemic effects, among which are an increased release of insulin, causing hypoglycemia.

The compliment system is the important part of the human defense system against human pathogenic organisms. Activation of this system by a pathogen may result in opsonization for phagocytosis, releases the anophylotoxin and formation of the membrane attack complex. Pertussis toxin is an oligonucleatide AB-type exotoxin that is the main factor for whooping cough. It mainly causes T-cell lymphocytosis and causes lysis [7]. It also causes hypoglycemia, increased IgE synthesis and increases histamine and endo toxin sensitivity. When the organism is in side body it inhibits leukocyte activities which include phagocytosis, chemo taxis and NK cell killing. Adenylate cyclase toxin penetrates the host cells, is activated by the calmodulin (calcium binding protein) and catalyzes the conversion of ATP to cAMP.

The expression of the virulence factors in B.pertussis is regulated by the bvg locus that codes for regulatory proteins BvgA and BvgS (originally called BvgABC). The BvgS protein contains an amino-terminal domain to senses external signals. The signals are transduced through the transmembrane domain to the cytoplasmic portion of BvgS which is thought to activate the transcriptional activator BvgA [2] by phosphorylation.

Transcription at the bvg locus of B.pertussis is controlled by four promoters they are PI, P2 and P3 promoters direct mRNA synthesis of the bvg operon and the P4 promoter directs the synthesis of an RNA complementary to the 5'untranslated region of the bvg mRNAs [5]. All the promoter are (PTx, adenylate cyclase and filamentous haemagglutinin) regulated by environmental factor. Toxin that is a pertussis toxin, PTx which mediate both the colonization and toxem stage of the disease. It contains two components A and B. A or S1 subunit is an ADP ribosyl transferase. The component B contains five polypeptide subunits S2-S5. These proteins bind to specific carbohydrate of the cell. PTx is transported from the site of growth of the bacterium to different susceptible tissue of the host.

When the B component binds to the host cell, the A subunit is entered in to the cytoplasm. PTX express a wide variety of different biological activities. They promotes the induction of morphological changes in the target cell, exotoxin secretion, stimulation of lipolysis, the activation of pancreatic islate cells, sensitization of histamine, induce lymphocytosis. PTX is therefore called as islet-activating protein, histamine sensitization factor and lymphocytosis promoting factor [10].

The A subunit gains enzymatic activity and transfer the ADP ribosyl of NAD to the membrane-bound regulatory protein Gi which normally inhibits the eukaryotic adenylate cyclase. Inactivated Gi protein cannot perform its normal function i.e adenylate cyclase inhibition [5]. The conversion of ATP to cyclic AMP is there. Intracellular levels of cAMP increase. This will disrupt cellular function. The phagocytosis got activated and activities such as chemo taxis engulfment, the oxidative burst, and bacteridcidal killing stimulated [1, 2].the effect of toxin in host includes lymphocytosis and alteration of hormonal activities. Insulin production increases and histamine got more sensitized.

The affected persons through 3 different stages:

Stage1: This stage is often same as the common cold. Symptoms include: mild to moderate runny nose and a slight fever. At this point the body is beginning its immune response. This is the stage where it is very easy for the bacteria to spread because the patient is unaware of the infection he is suffering (Catarrhal Stage) [4].

Stage2: This is the stage in which the severity of the infection is more sever. The coughing, sneezing and runny nose increase in severity. Chest spasms that result in coughing are followed by a large intake of air, causing the whooping sound. Vomiting after bronchiole spasm (coughing) episode is common because the violent shaking in the chest cavity. Attacks are most commonly seen at night and sleep apnea (not breathing while sleeping) often follows an episode. In between episodes the patient may appear normal and healthy. This stage lasts one to three weeks and begins subsiding in severity after two to three weeks (Paroxysmal Stage) [4]

Stage3: It lasts for 2 to 6 week but can last up to several months. During this time the number and severity of the coughing episodes decrease, until they are completely gone. Complications of whooping cough can include: pneumonia, bradycardia (heart beat of less than 50 beats per minute), apnea, conjunctivitis (infection of the membrane around the eye), loss of weight, ear infection, dehydration, collapsed lung, burst capillaries in the eyes, nose and face (causing nosebleeds, bruising around the eyes, etc.), cerebral hemorrhaging [4] and brain damage due to oxygen .Some of these side effects are potentially fatal, mainly in infants (Convalescent Stage).


The agent of whooping cough is mainly transmitted via droplets. Infections mainly result in the colonization and rapid multiplication of bacteria on the mucous membrane of respiratory tract. These bacteria can only be attached in the ciliated cells not in the non-ciliated part. The adenylate cyclase (cyaA) produced by Bordetella pertussis is the main causes cough [7]. CyaA is a 1760 residue long protein which has a unique mechanism to penetrate in to the host cells. CyaA first invade to the host cell and then activated by calmoduin (calcium binding protein) to produce supra physiological level of cAMP. αMβ2 integrin receptor at surface of the target cells[7]. The C-terminal is of CyaA made up of 40 nonpeptide motifs which is known as RTx (repeat in toxin) is involved in the interaction of the integrin receptor [7]. The central region of CyaA got inserted in to the plasma membrane. The N terminal catalytic region directly crosses the membrane and traslocated into cytosol of cells. The receptor integrin were then presented to the MHC-I and MHC-II molecule to elicit responses CD11b/CD18 integrin of T cell responses.

Fig1: showing the mechanism of CyaA inside the host cell. (C-terminal part (red), the central region (blue), N-terminal catalytic domain (green)) [7]. receptor is αMβ2 integrin.

Fig2: Model of CyaA action on the target cell membrane that followed by CD11b/CD18 receptor. [10]

Fig 2: shows how the bacterial toxin bound to the host cells [6].Receptor is αMβ2 integrin and different subunits of toxin PTx.

The receptor αMβ2 normally present in the cell helps in inflammatory responses inside body. The CyaA help in the activation of the IL-6 in the trachea which is affected by B.pertussis.[10]. When IL-6 got bind to the hypothalamus of the host the body temperature increases.


1. Todar, K. 2005.The Microbial World Lectures in Microbiology by Kenneth Todar PhD University of Wisconsin-MadisonDepartment of BacteriologyPertussis (Whooping Cough).

2. Rappuoli,R. 1991.Sequential activation and environmental regulation of virulence genes in Bordetella pertussis.vol.10 no.12 pp.3971 -3975. You accessed October 15, 2010.

4. KatieMcCorkle, BordetellaPertussis,

[Online] Date: May 13, 2009.

5. Kenneth C. Bagley,{dagger}, Sayed F. Abdelwahab,{ddagger}, Robert G. Tuskan, Timothy R. Fouts and George K. Lewis.2002.Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway,ed 72,pp.962-969.

6. Bordetellapertussisthebacteriumthatcauseswhoopingcough

7. Dr CHENAL Alexandre / Dr KARIMOVA Gouzel / Dr WOZNIAK Anna, Biochemistry of MacromolecularInteractionsCNRSURA2185.

[ONLINE] publication 2006.

8. Finger H, von Koenig CHW (1996). "Bordetella". In Barron S, et al.. Barron's Medical Microbiology (4th ed.).UnivofTexasMedicalBranch.

ISBN 0-9631172-1-1.

9. Plaut RD, Carbonetti NH (May 2008). "Retrograde transport of pertussis toxin in the mammalian cell". Cell. Microbiol. 10 (5): 1130-9.


Rheumatic fevere:

Swagatika Nanda

13 Oct 2010


Rheumatic fevere is a multisystem inflammatory disease which causes due to the group of infections by streptococcus pyogenes. It is mainly belived that rheumatic fevere is an antibody cross reactivity disease which occurs mainly after 2-4 weeks of the strep throat infections. This fever is named so because the symptoms are very much similar to the rheumatism (medical term affecting the joints and connective tissues). It is more like an autoimmune disease in which the self antibody causes harms to host. Mainly infections involve connective tissue of heart, joint, skins and vessel. It often leads to cardiovascular disorders.

Review of literature:

Rheumatic fevere (RF) is a fatal disease. The streptococcus pyogenes is the main culprit in this disease and it mainly affects the heart, vessels, muscular tissues, and joints of the body. The initial signs are Migratory polyarthritis which involve knee, elbows, wrist, ankle, sometimes hips and small joint of hand and feet [2]. Late and serious manifestation of is carditis is the inflammation of heart and its surrounding. The infection can affect exo, meso, and endocardium. Endocarditis is most common in case of GABHS (Group A β Haemolytic Bacteria) streptococcus leading permanent heart diseases [1]. The antibodies which the immune system generates against the M protein may cross react with cardiac myofiber protein, myosin of heart muscle glycogen and smooth muscle cells of arteries. It induces cytokine release and tissue destruction. Myocardium disease is inconsistent and may range from congestive heart failure which is fatal. Sometime it leads to atrioventricular conductions. The inflammation occurs through direct attachment of compliment of Fc receptor-mediated involvement of macrophages and neutrophils [2]. Sydenhams's chorea (SC) is a late manifestation of RF. It is characterized by sudden violent involuntary movement of the hand, feet and face muscles by the autoimmune on the CNS (Central Nervous System). Motor symptoms affected by SC is include Ballismus (violent involuntary rapid and irregular movements), facial grimacing (motor disorder), gross fasciculation of tongue [2] loss of fine motor control, tic (A tic is a sudden, repetitive, non-rhythmic motor movement or vocalization involving discrete muscle groups) etc. In addition to chorea, the acute attack is almost always characterized by psychiatric symptoms such as irritability, obsession and compulsion [1]. Diagnosis of SC is more difficult due to the presence of lower frequency of streptococcal antibodies. The life threatening complication of RHF is valvulitis. Vulvular lesion and aortic regurgiation are the most common events caused by valvulitis. Effective treatment of strep throat can prevent RF. Treatment of Rheumatic fevere include penicillin, aspirin and other anti-inflammatory medicines, chronic treatment of PCN 250 and sulphadiazin [2].


Bacteria activate the immune responses to eliminate bacteria. But sometimes the immune responses cross reacts with the body's own tissues because of the structural similarity of them. Molecular mimicry between streptococcal pyogenes M protein and human cardiac myosin protein leads to the auto immune reactions of the RF and rheumatic heart disease [2]. It is belived that both the cross reactive T-cells and cross reactive antibody plays the key role in this disease. Cardiac myosin has been shown as an auto antigen recognized by autoantibody of rheumatic patient. Cross reactive epitopes on S.pyogenes include the S protein and N-acetyle glucosamine. Monoclonal (T cells) antigens which are produced against these antigens cross reacted with the cardiac myocine and other cardiac proteins. Some other alpha-helical cardiac proteins include tropomyocine, keratin, laminin, vimentin [3].In many target organs such as synovium, neuronal tissue, subcutaneous and dermal tissue it causes damage. In the heart tissue, antigen-driven oligoclonal T cell expansions were the effectors of the rheumatic heart lesions. These cells are CD4+ and produces inflammatory cytokines (IFNγ and TNFα) [3]. It involves in the recruitment Th1, Th2 and Th17 cells. Carditis of acute rheumatic fevere is initialized by cross reacting antibodies that recognize the valve endothelium and laminin. Vascular cell adhesion molecule-1 is unregulated at the valve. It works for the infiltration (the diffusion or accumulation of substances in an excess amount which is not normal) and recruitment of these T-cells. The T cells initiate a predominantly TH1 response with the release of beta-interferon (IFN). Inflammation leads to neovascularisation (is the formation of functional microvascular network and red blood cell perfusion) which allows further employment of T-cells. The epitopes spreading in the valve and the T-calls responded against some other cardiac tissue like vimentin and tropomyosin. It leads to granular inflammation and causes chronic rheumatic heart disease. Rheumatic inflammation of heart affects the pericardium, the myocardium or the endocardium. These generally disrupt the electric conduction pathway [4]. These diseases are genetically determined as some human leukocyte antigen class II is involve in this. Other SNPs were also reported there association in RF.

Fig 1: the pathological mechanism of valvular inflammation in RF [4]. (IL: interleukin; VCAM: vascular cell adhesion molecule).

The effects of major histocompatibility complex (MHC)

Extra cellular antigens use the MHC molecules for the activation of body's immune responses. Cardiac myocine is one of the auto-antigen which is responsible for the Rheumatic lesions. The height amount of T cells infiltration is taken place by the cardiac myocine β chain. 34% of T cell clones are exhibited cross reactivity with different pattern. (a) Myocine and valve derived protein. (b) Myocine and streptococcal M5 peptide. (c) Myocine valve derived protein and M5 peptide [5]. The reactivates against the heart LMM protein. Cross reactive peripheral T- cell clones from a RHD patient gives responses to the recombinant M6 proteins, Cardiac myocine, tropomyocine and laminin. The cross reactive responses was MHC class1 and class2 restricted for the T cell clones are that were CD4+ and CD8+ respectively [6].These cells very efficiently recognize the M6 epitopes in the B region S2 and LMM region of cardiac myocine. INF-γ, TNF-α (inflammatory cytokinin) [5] and IL-10 are abundantly present in the cardiac walls, mainly the myocardium and valvular tissue. The lower IL-4 expressions are responsible for the progression of the Rheumatic heart disease and also cause damage to the heart valves.


Weil-oliver C; Rheumatic fever.Orphanet encyclopedia, January 2004, RHEUMATIC FEVER.

Faé KC, da Silva DD, Oshiro SE, et al. (May 2006). "Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease". J. Immunol. 176 (9): 5662-70 MECHANISM

Guilhermi, L.Jorge, K.03 october 2009.Rheumatic Fevere and Rheumatic Heart Disease: Cellular Mechanism Leading Autoimmune Reactivity and Disease.

Guilherme, L.,Ramasawmy,R,Kalil1,J.Rheumatic Fever and Rheumatic Heart Disease: Genetics and Pathogenesis.66:199-207. doi: 10.1111/j.1365-3083.2007.01974.x.



Epiglottis is the piece of cartilage at the back of the tongue. It has a very important function that is to close the wind pipe when swallowing. It keeps foods from entering the air way. It prevent cough and choke after swallowing. Epiglottities is the swelling which is a bacterial infection. Bacteria causing this are Haemophilus influenzae (H. influenzae). Some time it is also caused by many other bacteria and viruses. Epiglottities is begins with high fevere and is a medical emergency which seeks immediate medical help. This may causes respiratory obstruction and may fatal many times.

Review of literature:

Epiglottities also known as supraglottitis is the inflammation of epiglottis (a small flabby cartilage lid that covers the wind pipe) [2]. When epiglottis swells the lockage of windpipe is there and air cannot enter or exit the wind pipe. It is mainly caused by Haemophilus influenzae (is a gram negative bacterium) which is an aggressive microbe causes many serious diseases in children below 5yrs [1]. It is a life threatening condition causes suffocation and death. This bacterial disease is contagious. Sometimes the diseases can be caused by hot things that may injure the epiglottis which is also known as thermal Epiglottitis [1]. This may be result from eating solid foods, drinking hot liquid, or using illicit drugs various symptoms of Epiglottities are sore throat, difficulty swallowing, impaired breathing, upper respiratory infections, a muffled voice, hoarseness, fever, blue skin (cyanosis), chills and first heart beat [1].A high pitch whistling sound, called inspiratory stridor follows the characteristics coughing. This is very rare infections but life threatening.

About the microbe:

This microbe is very much virulent, because it related to the capsule formations by the bacteria. Usually type B serotype and its capsule polysaccharide, containing ribose, ribitol and phosphate. The capsule material is antiphagocytic. The bacterium can invade the blood or cerebrospinal fluid and don't attract the phagocytes. The polyribosyl ribitol phosphate (PRP) capsule is the most important virulent factor because it renders type b H. influenza resistant to phagocytosis by polymorphoneclear leukocytes in the absence of specific anticapsular antibody, and it renders type b H.influenzae resistance to phagocytosis by polymorphonuclear leukocytes in the absence of specific anticapsular antibodies. H influenza type b was entirely responsible for the host resistance to the infection. The outer capsule of bacteria constitutes of many proteins and revels several individual membrane proteins that may be associated with immunity. The use of polyribosyl ribitol phosphate (PRP) vaccine and, more recently, protein conjugated prp, has reduced vastly the frequency of the infection. The PRP vaccine contains of the type b capsular polysaccharide [2]. It elicits a strong primary antibody response, like most bacterial polysaccharide. H.influenzae type b Hib conjugate vaccine, coupled the polysaccharide to protein, induce memory type antibody responses. Bacterial capsules are long polysaccharide chains consisting of smaller repeating units. This repeating unit varies among bacterial species. Usually distinct among different serotypes of the same species. Capsular polysaccharide biosynthesis takes place in the cytoplasm; the resulting polysaccharide is then transported across the cytoplasmic membrane into the periplasm. After that they across the outer membrane to the bacterial surface. Capsules are substituted with phospholipids at the reducing end of the polysaccharide chains. According to the prevailing model, lipidation of capsular polysaccharide is required for transport across the inner membrane and possibly for anchoring to the outer membrane [1]. The genes responsible for the biosynthesis and surface expression of the type b capsule are located in the cap b locus, which contains three functionally distinct regions, similar to capsulation loci in other bacteria. Most isolates contain a partial tandem duplication of the cap b locus, with the two copies separated by a 1.2-kb bridge segment and flanked by IS1016 elements. The three functionally different regions of caps b locus are referring as the region 1 to 3. Region1 Region 1 contains genes designated bexA, bexB, bexC, and bexD and encodes an ABC transporter system involved in the export. Region 2 contains genes currently designated orf1 to orf4 and encodes enzymes involved in biosynthesis of ribose-ribitol-5-phosphate disaccharide subunits. Region 3 contains genes referred to as hcsA and hcsB, which share significant homology with genes in a number of other encapsulated pathogens [2].


Hib disease is spread through the air whenever an infected person sneezes or coughs. The virulent pathogen is also present there in the nose and airways in a patient who appears well. It contends with the ciliated epithelial cell defense of the respiratory tract. Adherent to this ciliated mucosa surface in first step in the pathway of transmission and establishment on a host. Haemophilus influenza produces ciliostatic substances which prevent the cilia from brushing the bacteria [4].These substances are produced only when the bacteria are established. During the pathogenic state the bacteria remains susceptible to serum protein that are antibiotics and compliments. Some bacteria have serum resistance by modification of their lipopolysacchride (LPS) O-antigen side chain, thus rendering them 'invisible' to the host immune defense. It can avoid the non-specific blood based defense of transferring; it limits the amount of bacteria-required Iron in the blood. The bacterium can steal back Iron from transferrin. Most of the strains belonging to Hi target carcinoembryonic (CEA) antigen, members of the immunoglobulin (Ig) super family. The CEA gene family comprises surface expressed (CEA) and secreted (progeny containing glycoprotein) subfamily [4]. The membrane associated subfamily is CEACAM1. All the protein contains an N-terminal domain of 108 amino acid residue [4]. Targeting of the CEACAM subgroup provides the organism with a wide tissue range for colonization and a means of host cell manipulation. Thus, divergent signaling mechanisms operate after ligation of bacteria with these receptors.


1. Emedicinehealth expert for everyday emergencies[online](updated 14 October 2010)available at 14 october 2010.

2. EuclidAve. S., LouisSt., June 2006. The Haemophilus influenzae Type b hcsA and hcsB Gene Products Facilitate Transport of Capsular Polysaccharide across the Outer Membrane and Are Essential for Virulence. Vol. 188, p. 3870-3877.



Corona virus infections:


Corona viruses are the group of virus which has a crown like appearances when viewed in under the electronic microscope. They belong to the Coronaviridiae family. Corona virus causes the Severe Acute Respiratory Syndrome (SARS) [4]. They are commonly known to cause the respiratory disease in human being. Some time they also caused the gastrointestinal disease in different farm animals. They contain positive single standard enveloped RNA as their genetic material. The genome of Corona virus is the largest among the viruses (27-32 nm in length). The virus is a Large, roughly spherical, enveloped particles with a nuleocapsids and large, petal like spike 20nm long, protruding from the membrane appearing as the crown [1].These viruses are host or tissue specific based on the receptor specificity of their spike or S protein. It is an enveloped viruses and the envelope is made up of glycoprotein [1].

Review of literature:

Virus is a microscopic particle inactive outside due to the incapability of replicating by their own. They take the help of the cellular mechanism for their own benefits. Human corona viruses of OC43 are generally occurs in the respiratory tract of the human being. The virus envelope is made up of S: Spike protein, receptor binding, cell fusion, major antigen, and major antigen, E: small envelope associated protein, M: membrane protein helps in budding and envelope formations, HE: Haemagglutinin-esterase and genome is associated with phosphoprotein N [2]. The virus primarily infects the upper respiratory human. Significant range of common cold is caused y this virus. Unlike to the rhinovirus the corona virus are difficult to grow in laboratory. Infection with corona virus causes the alteration in the transcription and translation patterns in the cell cycle. They interfere cytoskeleton, apoptosis, coagulation and inflammation and stress responses [3].

Fig 1: The structure of corona virus [3].

Fig1 shows the structure of corona virus which is having spike like structure glycoprotein (S). Membrane Glycoprotein (M), Nucleocapsid phosphoprotein (N). The M protein is the main virulent factor of the corona virus [3].

Mechanism of corona virus:

The host and pathogen interaction causes the disease. When once it entered in to the host body, the phases it follows replication and assembly. Fist in the cytoplasm the virus particle is uncoated and the RNA genome is liberated in to the host cytoplasm .The corona virus RNA contain a 5'methylated cap and a 3'polyadenylated-A tail to make it look as much like the host RNA. This helps the RNA to attach to the ribosome for translation. Infection cycle of CoV is started by the binding of the receptor ACE2. Human ACE2 (is a carboxy monopeptide) function as an efficient receptor for the 2002-2003 SARS-Co. ACE is widely found in the Central Nervous System[1].It is expressed with highest level in the lung, kidney, heart and gastrointestinal system. The entry of corona virus is mainly driven by the S glycoprotein which is a fusion protein of class1. The receptor binding domain in SARS-COV, S protein has been mapped to residues 318-510. It is determined in that different groups of corona virus the receptor domain occurs in different region of the S1 subunits [4].The ectodomain of the S2 subunit contain two heptad repeat (HR) regions. A sequenced motif of the containing coiled coil and a fusion peptide is predicted to be located immediately upstream of the fist HR region. The binding of the S1 subunits to the receptor can trigger a series of conformational changes of that may result in the formation of an antiparallel heterotrimeric six helix bundles by the two HR regions [1]. The structural changes of the S1 domain generate energy that drives the fusion of viral and cellular lipid membranes. In this process body cholesterol is appears to be an essential factor. The component essential for SARS-CoV infection is the angiotensin-converting enzyme 2(ACE2). SARS-CoV does not contain hemagglutinin-esterase-like attachment factor. It was found that the presence of L-SIGN allows very efficient entry of the virus. Some virus takes the path of endosome and some at the plasma membrane. The infection mediated by his virus could be inhibited by specific inhibitor of the pH-sensitive endosomal protease cathepsin L. Angiotensin I converting enzyme 2 is an exopeptidase that catalyses the conversion of angiotensin 1 to the nonpeptide angiotensin. The protein cleaved angiotensinI to angiotensin1-9, angiotensinII to angiotensin 1-7.It is belived to regulate the rennin-angiotensin system by counter balancing ACE activities [2] .Replication of the virus starts with the entry to the cell. Corona virus has a protein replicase in its genome that allows the RNA viral genome to be transcribed into new RNA copies using the host cells machinery. Fist the replicase protein is made when the gene encoding the replicase is translated. Then the translation is stopped by a stop codon. Corona virus transcription is involving a discontinuous RNA synthesis [1]. There is base pairing during transcription. N proteins of virus help RNA synthesis. It has RNA chaperone activity that may be involved in template switch. Corona virus initiates the translation by cap-dependent mechanism [2].