RESPON IMUN TERHADAP INFEKSI

Download Report

Transcript RESPON IMUN TERHADAP INFEKSI

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