Microbiology/Immunology lect.7 Dr. Mohammed A.K.AL-SA ADI
IMMUNITY TO MICROBES:
IMMUNITY TO VIRUSES:
Innate immunity:
The principal mechanisms of innate immunity against viruses are inhibition of infection by
1- type I IFNs(alpha and beta):Infection by many viruses is associated with production of type I IFNs by infected cells .Type I IFNs function to inhibit viral replication in both infected and uninfected cells .
2- NK cell –mediated killing of infected cells
Adaptive immunity:
1-Antibodies:It block virus binding and entry into host cells.
2-CTLs:It eliminate the infection by killing infected cells.
Evasion of immune mechanisms by viruses: 1-viruses can alter their antigens (antigen variation): Influenza virus show changes in antigenicity :antigenic drifts which are minor changes based on the mutations in the genome RNA .Antigenic shift which are major changes based on the reassortment of segments of the genome RNA .Because of antigenic variation, a virus may become resistant to immunity generated in the population by previous infection. 2-some viruses(e.g. CMV) inhibit class I MHC expressed on virus-infected cells. 3-Some viruses produce molecules that inhibit innate and adaptive immunity.EBV produce a protein that is homologous to IL-10 and may function to inhibit CMI. 4-Viruses may infect and either kill or inactivate immune cells.HIV infect CD4 T cells.
Immunity to bacteria:
Immunity to Extracellular bacteria:
Extracellular bacteria are capable of replicating outside host cells ,in the circulation ,connective tissues, and in tissue spaces such as airways and intestinal lumen:
Innate immunity:
1-complement system(alternative pathway)
2-phagocytosis
Adaptive immunity:
antibodies are the principal protective immune response against extracellular bacteria and function to eliminate the microbes and neutralize their toxins. The effectors mechanisms used by Ab include :Neutralization, opsonization of encapsulated bacteria ,and complement activation via classical pathway.
Immunity to intracellular bacteria:
intracellular bacteria are capable of replicating within phagocytes and other types of host cells.
Innate immunity: 1-phagocytosis initially by neutrophils and later macrophages 2-NK cells: function by two means direct killing of infected cells and by activating of macrophages by the production of IFN-gamma.
Adaptive immunity:
1-CMI:The protective immunity against such infection is cell mediated immunity(CMI),so individuals with deficient CMI ,such as AIDS patients are extremely susceptible to infection with intracellular bacteria ,fungi and viruses.CMI consists of 1-macrophage activation by TH1 cells which express CD40 ligand and secrete IFN- gamma .These two stimuli activate macrophages to produce several bactericidal substances which results in killing of phagocytosed microbes. 2-CTLs:which represented by cytotoxic T lymphocytes (CD8) T cells. Thus the effectors of CMI are CD4 T cells (TH1) that activate macrophages ,and CTLs function cooperatively in defense against intracellular bacteria such as mycobacteria, Listeria,… .
Immunity to parasites:
Innate immunity:
1-phagocytosis 2-complement
Adaptive immunity:
1-macrophage activated by IFN- gamma secreted by TH1 cells 2-ADCC mediated mainly by eosinophils and IgE and IgG
Evasion of immune system by parasites:
1-antigenic variation :parasites change their surface Ag during their life cycle in the infected host: e.g. Plasmodium 2-parasites become resistant to immune system during their resident in the host, schistosoma larva travel to the lungs of infected host and develop a thick tegument to resist the action of CTLs and complement system. 3-by living inside host cells 4-developing a thick cyst shedding their antigenic coats e.g. Entameoba histolytica 5-inhibition of host immune response buy induction of T cells anergy (in ability to response):filarial infection
Immunity to Fungi:
Innate immunity:
Phagocytosis by neutrophil and macrophages ,so patients with neutropenia or neutrophil dysfunction , are highly susceptible to fungal infection as in DM patients .
Adaptive immunity:
CMI activated by TH1 cells are the major mechanisms of adaptive immunity against fungal infection . Generally TH1 response are protective to the host during fungal infection TH2 response are detrimental to the host during fungal infection .This is due to the TH2 cytokines mainly IL-10 that inhibit CMI.