IMMUNITY AND INFECTIONS 1 : VIRAL

INTRODUCTION:

• To finally establish an infection, the pathogen has to deal with both innate and adaptive immunity.
• Our immune system recognize the pathogens as foreign with the help of antigens present on their surface.
• So, to evade the immunity, the pathogens initially try to escape the recognition by following the strategies as below:-

1. They grow inside the host cells so that they are sequestered from the immune attack.
2. They shade their membrane antigens to escape the recognition.
3. They camouflage by mimicking the surface of host cells so that they are not recognised as something foreign or different .
4. Some pathogens escape immune attacks by regulating the immune system and activating a branch of the immune system which is ineffective against them.
5. Many of them continually change their surface antigens, so that memory never works in their case.
6. Although vaccines and drugs have helped a lot to fight infections and even eliminate a few; but impaired immunity due to immunosuppressive drugs and infections from HIV has really worked to spread both rare and new diseases.

Based on the infections involved; there are:-

1)viral infections,

2)Bacterial infections,

3)Parasitic infections,

4)Fungal infections.

VIRAL INFECTIONS:

Introduction: viruses are segments of nucleic acids enclosed in a protein or lipoprotein coat.

typically, viruses preempts the biosynthetic machinery of the host to replicate it's own genome But, in many cases; the replication is error prone and generates numerous mutations.

Actually, from survival point of view, the virus is more likely to survive if it doesn't kill the host; but accumulating mutations give rise to strains which are harmful to the host and kill it.So now, virus requires to move to the new host .

virus is transmitted in the following ways:

1. The virus may become latent for a given period inside the host before death or illness; during which time the host may pass the virus to others.e.g.HIV
2. The virus can transmitt itself during even a short acute illness.e.g. influenza, small pox virus.
3. life cycle of viruses pathogenic for humans may also include nonhuman hosts. E.g. west nile virus. West Nile Virus replicates inside the birds and is carried by mosquitoes from the infected birds to humans or horses. They may also be passed between humans by blood transfusion and from infected pregnant mothers to their newborns.

Immune system against viruses:

INNATE IMMUNITY

• innate immune responses to viral infections primarily consist of interferons- alpha & beta and natural killer cells
• During it's life cycle, virus produces Ds RNA molecule which is detected by Toll-like receptors.This detection leads to expression  of IFN-alpha & beta by the infected cell.
• IFN-alpha and beta binds to their respective receptors and activates JAK-STAT pathway, which in turn induces the transcription of several genes.
• one of these genes encodes an enzyme known as 2'-5'-oligoadenylate synthetase which activates RNAse L that degrades viral RNA.
• other genes  inhibit viral replication.e.g. a specific protein kinase called dsRNA-dependent protein kinase (PKR) is induced which leads to inactivation of protein synthesis thus blocking viral replication in infected cells.
• Binding of IFN-alpha & beta to NK cells induces lytic activity ;making them very effective in killing virally infected cells.

ADAPTIVE IMMUNITY
Humoural immunity:(before virus attaches to host cells)

• Viruses have receptors which help them bind to molecules present on the surface of host cell.e.g. influenza virus binds to sialic residues of glycolipids or glycoproteins present on the host surface, EBV binds to type 2 complement  receptors on B cells.
• So, antibody again these receptors can be produced to block infection by preventing the binding of viral particles to the host cells.IgA in mucous secretions function in a similar way. The oral polio vaccine produces secretory IgA and block the attachment of poliovirus along the gastrointestinal tract.

Humoural immunity:(after virus attaches to the host cells)

• After virus attaches to the host cell, it tries to penetrate the host. 
• Antibodies can block the penetration by binding to epitopes which helps to mediate the fusion of the viral envelope with the host membrane.
• If the induced antibody is of complement activating type. Then, virus can be lysed or opsonized for phagocytosis to eliminate it.

Cell mediated immunity against viruses:

• Humoural immunity works in case of acute infections; but in case of latent state, CMI acts.
• Activated T-helper(1) cells produce a number of cytokines like IL_2,IFN-gamma, and TNF.
• In most viral infections; specific CTL activity arises in 3 to 4 days after infection, peaks by 7 to 10 days and then declines in later days.
• In initial days, IL-2 and IFN-gamma activate NK cells, which works to fight viruses until a specific CTL response develops; which then eliminates virus-infected self cells and thus eliminate potential sources of new virus.

EVASION OF HOST IMMUNE RESPONSES BY VIRUSES:
viruses follow the given strategies to evade immune response:
1)Encoding proteins
2)Targetting MHC
3)Evasion of complement mediated destruction
4)Change in antigens
5)Immunosuppression

1)Encoding proteins

• A number of viruses encode proteins that interfere with host defenses. e.g. hepatitis C virus blocks or inhibit the action of PKR which helps inhibit the viral replication.

2)Targetting MHC

• E.g. herpes simplex virus produce an early protein called ICP47.ICP47 inhibits TAP which is needed for antigen processing
• Adenovirus downregulate class 1 MHC expression.
• CMV and HIV downregulate class 2 MHC expression.

3)Evasion of complement mediated destruction:

• E.g. vaccinia virus secretes a protein that binds to the C4b and thus the classical component of complement pathway gets blocked.
• Herpes simplex virus has a glycoprotein component that binds to the C3b component and blocks both the classical and alternative pathway.

4)Change in antigens:

• A number of viruses work to change their surface antigens so that memory never works against them and our immunity fails to genuinely protect us.e.g.Influenza , HIV and rhinoviruses.

5)Immunosuppression:

• A number of viruses evade immune responses by causing generalized immunosuppression, which in turn, is caused by direct infection of lymphocytes or macrophages and lysing or breaking them; or by causing a cytokine imbalance.
• e.g. EBV produces a protein called BCRF1 that suppresses cytokine production by T-helper (1) cells resulting in decreased levels of IL-2, TNF and IFN-gamma.

Viral infections can be exemplified through INFLUENZA explained below.. http://biomaniac9.blogspot.com/2016/03/influenza-as-example-of-viral.html