Buhllar immune system Flashcards
The bacterial immune system is termed ___
CRISPR-Cas
Explain the type II CRISPR-Cas system in adaptive nucleic acid restriction
- Foreign DNA is recognized by Cas1 and Cas2 and is processed into a new spacer sequence within the CRISPR array (remember, crispr has repeated sequences of DNA with spacers in between the repeats)
- To restrict foreign DNA, the CRISPR array is transcribed as a single transcript (pre-cRNA array) and matured into small targeting crRNAs in a process requiring RNAse III and tracrRNA. The dsRNA complex of crRHNA and tracrRNA is associated with Cas9 and the spacer sequence within the crRNA can hybridie to complementary DNA sequences.
- Cas9 then mediated cleavage of the targeted DNA downstream of the proto-spacer adjacent motif, or PAM. This allows for the removal of invading DNA
3 Non-specific defense mechanisms
a) mechanical barriers (eg. skin)
b) mucous membranes
c) phagocytic cells
Define immunity
the ability of an organism to recognize and defend itself against infectious agent
susceptibility
opposite of immunity. Vulnerability of host to harm by infectious agents
Define immunology
study of adaptive immunity and how the immune system responds to specific infectious agents and toxins
Features of immune system
- Recognition: differentiate between self and non-self
- Specificity: ability to respond to various antigens in a specific manner
- Immunologic memory:exposure of immune system to an antigen leaves an imprint that primes the cells to respond in an antigen specific fashion in the future
Where does the process of tolerance take place?
in the BONE MARROW and THYMUS. Removes those lymphocytes that have receptors for self antigens
Primary and secondary lymphoid tissues
primary: bone marrow and thymus
Secondary: spleen and lymph nodes
all cells of the immune system are initially derived from:
bone marrow
B cells are produced by
bone marrow
What types of cells are produced by the thymus?
mature T cells
Immature ___ also known as prothymocytes, leave the ___ and migrate to the thymus to mature
Immature THYMOCYTES also known as prothymocytes, leave the BONE MARROW and migrate to the thymus to mature
When does the thymus reach its peak weight?
at puverty, after which point it begins to recede
function of the spleen
filter blood. Detect evidence of infectiuos agents or other contaminants. CRITICAL LINE OF DEFENSE AGAINST BLOOD PATHOGENS
Spleen is made up of which cells?
B cells, T cells, macrophages, dendritic cells, natural killer cells, and RBCs
____are filtered out of the lymph in the lymph node
antigens
if infection develops, what can happen to lymph nodes?
swelling
what are lymphocytes?
a type of WBC that makes antibodies and other substances that fight infection and disease.
Found in the blood and lymphatic tissue.
Attack viruses, bacteria and other microorganisms
B cell
- mature in the bone marrow and move into lymph nodes and spleen
- make antibodies in response to antigens
- antibodies bind to antigens, marking them for destruction
t cell
- mature in the thymus
- gather in lymph nodes and spleen
- directly attack foreign invaders and cancer cells.
- signal other immune system cells to areas where they are needed
- make lymphokines which activate other cells and substances
3 types of T cells:
- helper t cells stimulate B cells to make antibodies and help killer t cells work better
- killer t cells destroy cancer cells and cells containing foreign substances
- suppressor t cells make substances that help turn off the immune system response
Function of natural killer (NK) cells
- made in the bone marrow
- attach themselves to cells infected with croorganisms (ex. viruses and bacteria) and to cancer cells
What are granulocytes
white blood cells that fight infection
-contain granules filled with chemicals that hep destroy microoganisms and contribute to inflammatory and allergic responses
3 granulocytes
neutrophil, eosinophil, basophil
Neutrophil
- ingest and destroy bacteria, fungi, viruses, and other foreign cells by phagocytosis
- Body’s primary defense against harmful bacteria
eosinophil
- kill parasites
- play a role in allergic reactions
basophil
- release histamine and play a role in allergic reactions
- produce substances that attract neutrophils and eosinophils to an area to help fight infection
what are APCs and what do they do?
- Antigen-presenting cells
- surround foreign invaders and present the antigens from these foreign invaders to T cells and B cells for a response
2 APCs
phagocyte, dendritic cell
What are phagocytes?
-large EBCs that destroy foreign or damaged cells by phagocytosis
2 types of phagocytes
- monocyte
- macrophage (which produce cytokines)
Dendritic cell
type of WBC found in lymph nodes, skin and some organs. These ingest and break an antigen into pieces then stimulate T cells to destroy the antigen
T cells detect the presence of foreign substances by way of surface proteins called:
T-cell receptors
T helper cells are also called
CD4+ T cells
T killer cells also called
CD8+ T cells
define epitope
area on the molecule to which antibodies can bind
define hapten
small molecule that can act as an antigen if it binds to a larger protein molecule
Antibodies eliminate invading or foreign toxins by 3 mechanisms
- antibody enhanced phagocytosis
- complement mediated cell killing
- antibody-dependent cell killing (killer cells)
antibodies are produces by which cells of the immune system?
B cells
What happens when a B cell encounters the kind of antigen that triggers it to become active?
- it gives rise to PLASMA CELLS, which produce ANTIBODIES
- Plasma cells do not divide further and die after days of antibody production
structure of antibodies:
- consist of 2 heavy and 2 light chains held together by disulphide bonds
- carbohydrate attached to the heavy chain
5 classes of immunoglobulins
IgA IgD IgE IgG and IgM
Which is the major Ig in blood?
IgG
what does IgG do?
coats bacteria and the Fc binds to the receptors on the phagocytes
Which Ig can cross the placenta and protect newbrn?
IgG
which Ig exists as a pentamerand has 10 antigen binding sites?
IgM
Which Ig is good at activating the complement system?
IgM
Major Ig in secretions?
IgA: milk, tears, saiva, Gi tract and respiratory tract
IgA is important in __ immunity
local
Which is the least common Ig in the blood and what does it do?
IgE
Binds strongly to receptors on Mast cells and Basophils
-too much IgE is bad (allergic reactions)
humoral immunity : __ cells
Celular immunity: __ cells
humoral: B cells
cellular: t cells
define tolerance in the immune system
tolerance means the inability to generate a positive immune response to a specific antigen.
- usually achieved by prior exposure to specific antigens
- we are usually tolerant to self antigens
5 proposed major avenues through which an individual may develop an autimmune disease
- response to Ags that do not normally circulate in the blood
- A response to an altered Ag
- A response to an altered Ag that is shared or cross-reactive with self-Ags
- a mutation in immunocompetent cells to acquire a responsiveness to self-antigens
- a loss of immunoregulatory power by Th, Ts, and Tc cells
Is sjogrens syndrome systemic or localized autoimmune disease?
systemic
Myasthenia Gravis
- Ab-mediated autoimmune disease
- target antigen is alpha chain of the nicotinic acetylcholine receptor in the neuromuscular junction
- autoantibodies act as antagonist
- symptoms of muscle weakness, double vision,etc
Sjogren’s syndrome
- autoimmune disease affecting salivary glands, tear glands and other systems
- secondary disease can be associated with other disorders
- more common in females
- belueved to be triggered by a combination of genetic, environmental, and hormonal factors
- causes xerostomia, which leads to increased dental problems
- treatment of dry mouth with artificial saliva and drygs
Primary symptoms of sjogrens syndrome
dry eye and dry mouth (cracked tongue, sore throat, difficulty talking and swallowing, difficulty eating, increased cavities, mouth sores, cracked lips)
Two AIDS virus:
HIV-1 and HIV-2
Which HIV is predominantly found in Africa? Western World?
Africa - HIV-2
WW - HIV-1
Which is worse/more severe symptoms? HIV 1 or 2?
HIV-1 (in western world)
HIV is a retrovirus that contains reverse ____
transcriptase
HIV is cytopathic. What does this mean
it causes changes to infected cell
Shape of HIV and how many spikes?
spherical, 72 spikes
what do the HIV spikes contain?
the env gp120 and gp41 glycoproteins
gp120 binds to a receptors on ____. What occurs?
CD4 lymphocytes.
This stimulates proteolytic cleavage of gp120; exposes gp41 to fuse with a receptor on the lymphocyte surface
-HIV is internalized
Main difference between HIV 1 and 2
regulatory gene, vpu, is not present in HIV-2
HIV encodes for 3 structural genes:
a) group specific antigen (gag): p24, p7, p17
b) envelope (env): gp120, gp41
c) polymerase (pol): reverse transcriptase, integrase, protease
steps in the HIV replication cycle:
- fusion of the HIV cell to the host cell surface
- HIV RNA, reverse transcriptase, integrase, and other viral proteins enter the host cell
- viral DNA is formed by reverse transcription
- viral DNA is transported across the nucleus and integrates into the host DNA
- new viral RNA is used as genomic RNA and to make viral proteins
- new viral rna and proteins move to cell surface and a new, immature, HIV virus forms
- The virus matures by protease releasing individual HIV proteins
Importance of reverse transcriptase
- crucial for integration into host’s DNA
- HIV has a set of transactivators that control transcription; most important are tat and rev
- Tat stimulates and promotes elongation of transcripts
- rev acts at post-transcriptional level to regulate viral mRNA transport from the nucleus, and the splicing of long HIV transcripts
Which cell type doe HIV specifically attack?
t-helper cell, which coordinates the immune system’s response to infections
How does HIV gain entry to the t-helper cell?
by attaching itself to the CD4 protein on the surface of the cell. It then takes over the cell and replicates, seeking new T-helper cells to infect
4 stages of HIV
- primary HIV infection: patient unaware. 3 months into infection, might experience flu-like symptoms that subside within 2 weeks
- asymptomatic stage: no symptoms manifest, but virus remains active
- Symptomatic stage: individual feels unwell and experiences infections caused b bacteria and viruses
- AIDS: CD4 count is less than 200. Serious diseases
How to measure virus progression?
CD4 count
Why are CD4 cells important?
they induce B cell proliferation, induce Tc cell maturation, and perform other roles in the overall immune system
What is AZT?
- azidothymidine is an inhibitor of reverse transcriptase
- can depress HIV replication
- can cause bone-marrow depression i given for prolonged periods
CCR5
- protein on the surface of WBCs that is involved in the immune system as it acts as a receptor for chemokines
- many forms of HIV initially use CCR5 to enter and infect host cells
- the CCR5 receptor works with CD4 to allow the HIV to enter cells
- MANY PEOPLE WHO ARE RESISTANT TO HIV HAVE A MUTATION IN THE CCR5 GENE CALLED CCR5-deta32
- CCR5-delta32 mutation results in a smaller protein that isn’t on the outside of the cell aymore
Most forms of HIV cannot infect cells if there is no ___ on the surfface
CCR5
Deleting which gene can help individuals fight HIV infection?
CCR5
