DOSEN IMUNOLOGI FAKULTAS FARMASI UNIVERSITAS PANCASILA JAKART A RESPON IMUN TERHADAP ANTIGEN

Antigen Suatu substansi yang menyebabkan timbulnya respon imun bila masuk kedalam jaringan hewan/manusia yang peka dan mampu mengikat antibodi yg spesifik (biasany BM nya besar) Bentuk protein, polisakarida, lipida, asam nukleat atau material lainn yang juga dapat bersifat antigen Mikroba adalah antigen dan ia dapat memproduksi antigen Antigen mempunyai lokasi yg spesifik untuk mengikat antibodi disebut “epitope”

Immuniti dan Respon Immun Di bangun dari dua komponen sistem imun: Humoral atau circulating antibody system Sel B Cell mediated immunity  Sel-T

Immuniti dan Respon Immun Sistem imun mengidentifikasi antigen (protein asing dan polisakharida)  Komponen dr mikroba atau bagian partikel produk dr mo tersebut dan protein asing lainnya dan polisakharida. (termasuk asam nukleat) Hospes (manusia dan hewan) antigen tdk di bentuk oleh individu juga sebagai antigen  Result: in graft, transplant rejection

Sistem imun Sistem imun manusia di mulai dari saat perkembangan embrio Di mulai pd saat proses hematopoietic stem cells. Stem cells differentiate menjadi sel yg penting dalam sistem imun  granulocytes, monocytes, dan lymphocytes Stems cells juga ber defernsiasi menjadi sel darah lain yg tdk terlibat dalam sistem imun, yaitu sel darah merah dan megakaryosit (fibrin) Stem cells terus menerus diproduksi dan berdeferensiasi sepanjang suatu masa kehidupan manusia

Produksi sel darah dan leukosit

Komponen sistem imun manusia

Sistem imun

Immuniti dan respon sistem imunm

Immuniti dan respon sistem imun

Seleksi clonal dr sel B krn stimulus antigenik

Klasifikasi Antibodi (Immunoghlobulins)

Respon imun terhadap antigen pd manusia

Respon imun terhadap antigen First exposure to antigen "A”:  begin to make low levels of antibody in about a week Second exposure to antigen "A”:  produces a much faster response, and  several orders of magnitude higher levels of antibody.  Ability of antibody to bind antigen also increases dramatically in the secondary response. Injecting a new antigen "B” with "A"  Elicits only a primary response  Shows that a memory or prior exposure is required for the accelerated response.

Humoral Mediated Immune Response Produces secreted antibodies (proteins) Bind to antigens and identify the antigen complex for destruction. Antibodies act on antigens in the serum and lymph B-cell produced antibodies may be  attached to B-cell membranes or  Free in the serum and lymph. Each B lymphocyte makes a unique antibody molecule (immunoglobulin or Ig) Over a million different B lymphocytes are produced in each individual  So, each individual can recognize more than a million different antigens

Immuoglobulin G (IgG)

Reaksi Immunoglobulin terhadap antigen IgG antibody molecule  Composed of 2 copies of 2 different proteins  Two copies of a heavy chain  >400 amino acids long  Two copies of a light chain -  >200 amino acids long each IgG antibody molecule can bind 2 antigens at one time  A single antibody molecule can bind to 2 antigens (e.g., viruses, bacateria or other particle), which leads to clumping

Pengaruh ukuran antgen terhadap respon antibodi

Fate of Antigen-Antibody Complexes Ag-Ab complexes engulfed into the B-cell and partially digested Antigen is displayed on the B-cell surface by a special receptor protein (MHC II) fo recognition by helper T-cells B-cell is activated by the helper T-cell to divide and produce secreted antibodies  Abs circulate in the serum and lymph Some B-cells become memory cells to produce antibody at a low rate for a long time (long term immunity)  They respond quickly when the antigen is encountered again  the response is regulated by a class of T-cells called suppressor T-cells

Cell-Mediated Immunity and T Cells T cell receptors are cell surface receptors that bind nonself substances on the surface of other cells Major histocompatibility complex (MHC) proteins protrude from the surfaces of most cells in mammals  They help to distinguish self from nonself  They coordinate interactions among lymphocytes and macrophages Cytokines are soluble signal proteins released by T cells  They bind and alter the behavior of their target cells

Cell Mediated Immune System: T lymphocytes T-cells mature in the thymus (thus the name T-cell) Act on antigens appearing on the surface of individual cells. Over a million different kinds of T-cells  Each produces a different receptor in the cell membrane  Each receptor is composed of 1 molecule each of two different proteins  Each receptor binds a specific antigen but has only one binding site  Receptor only recognizes antigens which are "presented" to it within another membrane protein of the MHC type (major histocompatibility complex)  Recognizes specific antigens bound to the antigen- presenting structures on the surface of the presenting cell.  Recognizes antigens presented by B-cells, macrophages, or any other cell type

T Cells and their Functions Have a specific receptor for a fragment of antigen Cytotoxic T-cells:  Contain a surface protein called CD8  Destroy pathogen infected cells, cancer cells, and foreign cells (transplanted organs) Helper T-cells:  Contain a surface protein called CD4  Regulate both cellular and humoral immune systems  This regulation reduces autoimmunity.

Autoimmune disease Self immunity Some examples:  rheumatic fever  rheumatoid arthritis  ulcerative colitis  myasthenia gravis  Lyme disease (microbial etiology)  Guillan-Barre syndrome (microbial etiology)  Reiter’s syndrome or reactive arthritis (microbial etiology)  Insulin dependent diabetes mellitus (IDDM) (microbial etiology?)

Respon Interaksi diantara komponen sistem imun T-cells, B-cells, and macrophages use MHC-II receptors for presentation; All other cells use MCH-I  (responsible for most of tissue graft rejection) When a T-cell is presented with an antigen:  its receptor binds to the antigen and  it is stimulated to divide and produce helper T-cells  activate B-cells with bound antigen suppressor T-cells  regulate the overall response Cytotoxic "killer" T-cells  kill cells with antigen bound in MHC-I

Peran Immuniti terhadap infeksi lokal Immunity to infection is usually short-term and transient – Mucosal (secretory or IgA) immunity in the gut or respiratory tract wanes over time Proof of concept: live, oral rotavirus vaccine: – immunity declines over time and reinfection with “wild” type rotaviruses occurs Repeated localized (e.g., gastrointestinal) re-infection is possible. Examples: – Viruses: rotaviruses, noroviruses, adenoviruses and some enteroviruses. – Salmonella spp, Shigella spp., Campylobacter spp, and E. coli spp. cause localized infections – Giardia lamblia and Cryptosporidium parvum

Peran imuniti terhadap infeksi sistemik Immunity against generalized/systemic/disseminated infection is usually lifelong, unless immune system is severely compromised Localized (e.g., gastrointestinal) re-infection is possible Hepatitis A and E and many enteroviruses are viruses causing systemic/generalized/disseminated infections Salmonella typhi is a bacterium causing systemic infection Typically, immunity against severe illness is long-term and probably lifelong – Proof of concept: live, oral poliovirus vaccine and poliomyelitis eradication; susceptibles are newborns and infants Antigenic changes in microbes may overcome long-term immunity and increase risks of re-infection or illness

Seleksi infeksi mikroba strain baru thdp kepekaan dan terjadinya penyakit Antigenic changes in microbes overcome immunity, increasing risks of re-infection or illness – Antigenically different strains of microbes appear and are selected for over time and space – Constant selection of new strains (by antigenic shift and drift) – Partly driven by “herd” immunity and genetic recombination, reassortment, bacterial conjugation, bacteriophage infection and point mutations Antigenic Shift: – Major change in virus genetic composition by gene substitution or replacement (e.g., reassortment) Antigenic Drift: – Minor changes in virus genetic composition, often by mutation involving specific codons in existing genes (point mutations) A single point mutation can greatly alter microbial virulence

Perubahan sifat antigenik (mutasi) pada virus influenza H5N1 reasortmrnt