Immune Response to Infection

Infectious Agents

• Viruses• Bacteria• Parasites• Protozoa

Primary response:

• Natural Killer Cells: – Non-antigen specific.– These cells attack any foreign microbe in the

body and attempt to kill it.• Macrophages: – Respond to all invading microbes, ingest and kill. – Presents antigens from the microbe cell wall on

the external cell wall of the microphage to activate T cells.

Secondary response:

• B Cells respond to antigens by differentiating into plasma cell.

• Plasma Cells: – Secrete one specific antibody for a particular

antigen based on the cell line from the B cell.• Helper T Cells: – Secrete interleukin hormone to stimulate clonal

growth of activated T and B cells.

Tertiary response:

• Cytotoxic T Cells: – Bind to body cells infected by the microbes and

secrete toxic substances killing cell and invader.• Antibodies: – Complex with antigen which aggregates microbes

together to deactivate the organisms.

Viral Infections

Overall Response to Viral Infections

Innate Immune Response

T cell activationDCs can be directly infected by virus.If DCs are not infected by virus, DCs can still internalize viral antigens from the suroundings through phagocytosis, endocytosis and macropinocytosis. The antigens can be presented in the context of both class II and class I MHC through cross-priming.

virus

DC

infection

Viral antigen EndocytosisPinocytosisphagocytosis

Ag-MHC I

Ag-MHC II

CD8 T cell

CD4 T cell

CTL

TH1

TH1 failitates CD8 T cellactivation by producing IL2and activation of DCsthrough CD40L-CD40

IL12IFN-

DCs are activated by recognition ofViral PAMPs through TLRs.

Secondary lymphoid tissues

Lysis of infectedcells

B cell activation

Viral antigen B cell

Antigen-antibodycomplex

Naturalantibody

B1 cells

FDC

TH cellsDC

B cell activation antibodies

Seoncdary lymphoid tissues

Antibody Interaction with Viruses

• Neutralize• Advantage antibodies to be at site of entry –

mucosal surface• Secretory IgA in mucous secretions plays an

important role in host defense against viruses by blocking viral attachment to mucosal epithelial cells

Viral Response to Host Immune Response

• HCV (Hepatitis C Virus) Evades Anti-viral Effect Of IFNs By Inhibiting Action Of PKR

• HSV (Herpes Simplex Virus) Decreases Expression Of MHC I, Avoids CTL Elimination

• CMV (Cytomegalovirus) Also Decreases Expression Of MHC I

• HIV (Human Immunodeficiency virus) Decreases MCH II Expression, No TH1 Support for CTL

• Influenza Virus, Keeps Changing Antigens– Antigenic Drift– Antigenic Shift

Bacterial Infections

Bacterial Infections• Bacterial Infections Are Eliminated By Humoral Immunity– Exception: intracellular bacteria Ex. TB– DTH Is Important In Elimination Of Intracellular Bacteria– Antibodies Eliminate Bacteria Or Bacterial Toxins

• Opsonization Of Bacteria• Neutralization Of Toxins

– Exotoxins (Ex. Diptheria)– Endotoxins (Ex. LPS)

• Lysis Of Bacteria Thru Complement Pathway• Complement Activation Thru Mast Cell Activation Results In Localized

Inflammation– Vasodilation and Extravasation (Neutrophil Accumulation)

• Bacteria Enter Host Thru– Respiratory Tract, GI Tract, Genitourinary Tract, Skin

Bacteria Evade Host Defense Mechanisms

• Bacterial Infection Involves 4 Steps– Attachment– Proliferation– Invasion Of Host Tissue– Toxin Induced Damage To Host Cells

• Attachment– Some Bacteria Have Pili– Some Bacteria Secrete Adhesion Molecules (Bordetella Pertussis)– Immune System Response To Attachment Is IgA

• Prevents Attachment• Some Bacterial Evade IgA Thru Proteases That Decrease ½ Life Of IgA

– Ex. Heamophilus Influenzae• Some Bacteria Avoid Phagocytosis By Surrounding Themselves In A

Polysaccharide Capsule. Ex. Streptococcus Pneumoniae

• Overzealous Immune System Can Be Pathogenic– Bacterial Septic Shock

• Predominant Cytokines Involved: IL-1 and TNF-• Source: M

– Intracellular Bacteria Cause Granulomas• Extensive Tissue Damage• Ex. Tuberculosis

• Tuberculosis (Mycobacterium Tuberculosis)– 3 Million Fatalities Every Year Globally– M Ingest M.T But Cannot Digest It– Eventually Burst Releasing Bacilli– M And TH1 Cells Form Granulomatous Lesion,

Containment+Destruction Of Healthy Tissue– INF- and IL-12 Are Crucial In Eliminating Pathogen

Immune Response Against Pathogen Can Cause Pathogenesis

Immune Response to MTb• CD4+ T cells are activated within 2–6 weeks after infection.• Infiltration of large numbers of activated macrophages. • Wall off the organism inside a granulomatous lesion called a tubercle . • A tubercle consists of a few small lymphocytes and a compact collection

of activated macrophages, which sometimes differentiate into epithelioid cells or multinucleated giant cells.

• The massive activation of macrophages that occurs within tubercles often results in the concentrated release of lytic enzymes. These enzymes destroy nearby healthy cells, resulting in circular regions of necrotic tissue, which eventually form a lesion with a caseous (cheeselike) consistency

• As these caseous lesions heal, they become calcified and are readily visible on x-rays, where they are called Ghon complexes.

Protozoan Diseases

• Protozoans are unicellular eukaryotic organisms:-– Amoebiasis, Chagas’ disease, African sleeping sickness, malaria,

leishmaniasis, and toxoplasmosis. • The type of immune response that develops to protozoan

infection and the effectiveness of the response depend in part on the location of the parasite within the host.

• Many protozoans have life-cycle stages in which they are free within the bloodstream - humoral antibody is most effective.

• Many of these same pathogens are also capable of intracellular growth- cell-mediated immune reactions are effective in host defense.

Diseases Caused by ParasiticWorms (Helminths)

• Unlike protozoans, which are unicellular and often grow within human cells, helminths are large,multicellular organisms that reside in humans but do not ordinarily multiply there and are not intracellular pathogens.

• Although helminths are more accessible to the immune system than protozoans, most infected individuals carry few of these parasites for this reason, the immune system is not strongly engaged and the level of immunity generated to helminths is often very poor.

Schistosomiasis Mansoni• More than 300 million people are infected with Schistosoma, a

trematode worm that causes a chronic debilitating infection.• Infection occurs through contact with free-swimming infectious

larvae, called cercariae.• When cercariae contact human skin, they secrete digestive

enzymes that help them to bore into the skin,where they shed their tails and are transformed into schistosomules.

• The schistosomules enter the capillaries and migrate to the lungs, then to the liver, and finally to the primary site of infection, which varies with the species. S. mansoni and S. japonicum infect the intestinal mesenteric veins.

Immune Response against Viruses

Immune Response against Bacteria

Immune Response against Parasites/Worms