Lecture 17 Flashcards
How many major HLA genes are needed for most transplants to succeed?
4
HLA genes
account for about 50% of the genetic impact on immunity
what determines an HLA type
several genes with multiple alleles
Major histocompatibilty complex
MHC region on short arm of chromosome 6 containing about 70 genes
what encodes human leukocyte antigens (hla)
MHC class I and II
what is the difference between class I and II HLAs that encode human leukocyte antigens?
Class I - encode antigens defining “self”
Class II - encodes several proteins found in antigen-presenting cells
MHC class III genes
encode protein providing non-specific immune functions
the human immune system
a network of vessels called lymphatics and bean-shaped structures called lymph notes
what is lymph and what does it carry
the fluid filling the lyph ducts
-carries macrhopages and B- and T- lymphocytes
what organs are involved in production or maturation of immune cells
spleen and thymus
bone marrow
immunity
the immune response attacks pathogens, cancer cells and transplanted cells with two lines of defense
1) innate immunity
2) adaptive immunity
difference between innate and adaptive immunity
- innate immunity - immediate and generalized
- adaptive immunity - specific and slower
these act after various physical barriers block pathogens
physical barriers
The first line of defense Examples include: - Unbroken skin - Mucous membranes and secretions - Waving cilia of the respiratory tract - Flushing effect of tears, saliva, urination, and diarrhea All of these are non-specific defenses
a central part of innate immune response - inflammation
- A process that creates a hostile
environment for pathogens - Sends in phagocytes that engulf and destroy pathogens via phagocytosis
innate immune response
OInflammation Collectins - Recognize specific bacterial antigens Cytokines - Interferon = Anti-viral - Interleukins = Fever-inducing - Tumor necrosis factor α = Anticancer
Cytokines also play a role in adaptive immunity
what immunity do cytokine play a role in?
adaptive and innate immunity
complement system (innate immune response)
- Plasma proteins that assist or complement other defense responses - Roles of complement proteins include: Puncture bacterial cells Dismantle viruses Trigger histamine release to dilate blood vessels Attract phagocytes
adaptive immunity
Requires stimulation
Response time is in days
Has three basic characteristics:
1) Diversity: many different pathogens
recognized.
2) Specificity: distinguishes particular molecules.
3) Memory: responds faster with
subsequent exposure.
- Primary immune response: reaction to first exposure.
- Secondary immune response: reaction to exposure using “memory” of first response.
adaptive immunity - two types of response
1)Humoral immune response
- B cells produce antibodies in
response to activation by T cells
2)Cellular immune response
- T cells produce cytokines and
activate other cells
cytokines
- Interferon = Anti-viral
- Interleukins = Fever-inducing
- Tumor necrosis factor α = Anticancer
humoral immune response
- Antigen-presenting macrophage activates a helper T cell
- Helper T cell activates a B cell with matching cell surface receptors
- B cells divide to produce plasma cells and memory cells
- Plasma cells secrete antibodies into blood that will recognize the antigen presented.
- Memory cells remain dormant until second exposure when they respond faster and more effectively
humoral immune response - polylonal
polyclonal
-different antibody proteins recognize and bind to different features of foreign cells
antibody structure
Minimally consist of four polypeptide chains
- Two long (heavy) chains
- Two shorter (light) chains
- Constant region of each chain is similar
- Variable region of each chain is diverse
Antigen binding sites
- Idiotypes: sites in direct contact with antigen
- Epitope: portion of the antigen contacting the antibody
large antibody molecules
consist of two or five Y-shaped subunits
function of antibodies
- Bind pathogen protein or toxin and inactivates or neutralizes them
- Can clump pathogens making them more visible for macrophages
- Activate the complement system boosting the innate immune response
In some situations, the antibody
response can be harmful
another word for antibodies
immunoglobulines
-five major types distinguised by location and function
creation of antibody diversity
- During early development of B cells, sections of the antibody genes are rearranged along their chromosome
- Rearrangement due to enzymes cutting and pasting different combinations of V (Variable), D (Diversity), and J (Joining) genes creates new versions of the antibody proteins
genes and chains on the chromosomes
- V, D and J genes for heavy chains are on chromosome 14.
- V and J genes for light chains are on chromosomes 2 and 22.
cellular immune response maturation of T cells
- T cells must recognize foreign antigens and not recognize self antigens
- Immature T cells, called thymocytes, travel to the thymus and display their cell surface receptors
- The thymus lining displays self antigens
- T cells that bind these self antigens die by apoptosis
- T cells that do not bind the self antigens survive and mature
Thymocytes
immature T cells that travel to the thymus and display their cell surface receptors
what happens when T cells bind to self antiens
T cells must recognize foreign antigens and not self antigens because T cells that bind to self antigens die by apoptosis
-T cells that do not bind the self antigens survive and mature
Types of T cells
- Helper T cells - Have CD4 antigens
- Cytotoxic T cells - Have CD8 antigens
- Regulatory T cells - Secrete cytokines
Role of T cells in humoral immune response
- Recognize antigens presented by macrophages
- Helper T cells stimulate B cells to produce antibodies
Role of T cells in cellular immune response
- Secrete cytokines
- Activate cytotoxic T cell
types of cytokines - colony stimulating factors
stimulate bone marrow to produce lymphocytes
types of cytokines - interferons
block viral replication, stimulate macrophage to engulf viruses, stimulate B cells to produce antibodies, attack cancer cells
types of cytokines - interleukins
contol lymphocyte differentiation and growth, cause fever that accompanies bacterial infection
types of cytokines - tumor necrosis factor
stop tumor growth, releases growth factors, stimulates lymphocyte differentiation, dismantles bacterial toxins
cytotoxic T cells
Continuously monitor body cells, recognizing and eliminating virus-infected and tumor cells
abnormal immunity
immunity may be too weak,
too strong, or misdirected
Abnormal immune responses may be multifactorial or caused by a mutation in a single gene
inherited immune deficiencies
At least 20 types
Affect innate and adaptive immunity
Examples
- Chronic granulomatous disease:
Mutation of oxidase enzyme results in neutrophils that cannot kill bacteria
- Severe combined immune deficiency (SCID): Impacts both humoral and cellular immunity due to lack of mature B cells and/or T cells
immune system cells - macrophages
presents antigens
performs phagocytosis
immune system cells - mast cell
releases histamine in inflammation
releases allergy mediators
immune system cells - b cell
matures into antibody producing plasma cell or into memory cell
immune system cells - helper t cells
- recognizes nonself antigens presentd on macrophages
- stimulates B cells to produce antibodies
- secretes cytokines
- activates cytotoxic T cells
immune system cells - cytotoxic
attacks cancer cells and cells infected with viruses upon recognizing antigens
immune system cells - natural killer
attacks cancer cells and cells infected with viruses without recognizing antigen; activates other white blood cells
immune system cells - suppressor
inhibits antibody production
