Episode 24: Doctor Dan gives part 2 of his Cancer lecture series available in full at www.Medical-Mastermind-Community.com.
Xeroderma pigmentosa – sun exposed areas, auto recessive, can cause all skin cancers (BCC, SCC, and melanomas), and the defect is in DNA repair enzymes. Other DNA repair defects are associated [...]
Told to know these for “passage of the exam”
Autograph- skin transplant; no immunosuppression
Syngenic or Isograft- identical twins
Allograft/Homograft- genetically different of same species; need immunosuppression
Xenograft/Heterograft- 2 different species
Primary and Secondary Allograft rejection
T cell mediated - memory and specificity
First set rejection- (7-30 days)- organ and tissue allografts are rejected by non sensitized recipients in an [...]
Introduction
HLA= Human Leukocyte Antigen
Located on Chromosome 6
3 groups of proteins (I,II,III)
Class I
A,B,or C
Class II
DP,DQ,DR
Class III
complement components (C4, B1, C2)
MHC Class I Molecules
Location- A,B,C
associated w/ b2-microglobulin on cell surface
co-dominant (half from mommy and ½ from daddy)
with b2-microglobulin forms 4 domains
binds oligopeptides
the a.a. [...]
Immunity- “to protect”
Purpose- to distinguish between self and non-self; destroy non-self
Acquired Immunity- response of lymphocytes to an antigen. The emphasis in medical school is on acquired immunity.
History
Cowpox- Jenner- 1798
Attenuated Vaccines- Pasteur- 1880
Blood Groups- Landsteiner- 1900
Innate Immunity
all multicellular animals
NON-SPECIFIC!!!!!
Present at birth
Initial Barrier
Mediated by
Physical barriers, Phagocytic cells (non-specific), Proteins, [...]
Innate or Natural Immunity
1. Physiological barriers
Skin
Epidermis, Acid pH of sweat, lysozyme
Mucous membranes
Mucus, hydrolytic and proteolytic enzymes, Low pH in vagina and Stomach
2. Phagocytosis
General Properties
a. Stages
1. ingestion
2. formation of phagocytic vacuole (phagosome)
3. fusion of phagosome with lysosome
4. destruction of bacterium of virus
b. Opsonization- increases rate of phagocytosis
1. due to antibodies or [...]
Bacterial Ab (Immune complexes and Cytotoxicity)
Mycobacterial DTH and granulomatous reactions
Viral Ab (Neutralization), TCTL and DTH
Protozoal DTH and Ab
Worms Ab (Atopis, ADCC) and granulomatous rxns
Fungal DTH and granulomatous rxns
3 phases of response to initial infection:
1. Early, innate and non-specific response (0-4 hrs)
preformed effector cells and molecules
2. 4 hrs to 4 [...]
Goal: To recognize but not respond to self; to recognize and respond to non-self for a long enough period with enough intensity to result in immunomodulation
Development of B and T Cell Repertoire (How do we get the ammo?)
both B and T cells’ specificities are conferred via RANDOM gene rearrangement
We have a [...]
HIV
Hiv-1- most common in U.S. and Europe
HIV-2- prevalent in Africa (50% homology w/ HIV-1)
Retroviruses- from DNA from RNA genome
There are oncogenic (HTLV) and cytolytic (HIV)
Lentiviruses- slow acting cytolytic retroviruses (HIV)
HIV Genome and Structure
9000 bp segment of s.s. RNA
gene products are cleaved by HIV protease
Important [...]
Antigens (Ag)- substances able to induce a specific active immune response
Immunogens- are agents that are capable of inducing an immune response
Antigens- agents capable of binding specifically to components of the immune system such as lymphocytes or antibodies.
All immunogens are antigens, but not all antigens are immunogens
Some substances require another substance to couple to [...]
Definitions
1. immunodeficiency disorders- diverse group of illnesses which, as a result of one or more abnormalities of the immune system, predispose an individual to infection.
can involve malfunction of blood cells (lymphs, granulo., monos)
soluble molecules- (Ab, complement)
CAUSES
inherited genetic trait [...]
Immunoglobulins are found in large quantities in blood serum
The gamma region contains most of the Ab in an immunized individual
Heterogeneous
Structure of Light and Heavy Chains
4-chain structure
2 identical heavies and 2 identical lights
Light Chains
Two types of light chains, k and l.
the difference is in the amino acid sequence of [...]
Variable region genes are encoded by multiple exons on the same chromosome
Light chain variable region genes are produced by DNA rearrangements that join a VL and a JL gene from a pool of many such genes that are variable in sequence
Heavy chain variable regions are similarly produced but use a different [...]
I. Historical Aspects-
A. Fever was first recorded in ancient hieroglyphics several thousand years BC.
B. Hippocrates had a humoral theory about fever being a sign of ill health.
C. In 1868 Mr. Wunderlich developed the thermometer and established fever as one of the 4 vital signs.
D. Around 1900, Sir Wm. Osler described the “Three Great [...]
A system of more than 30 serum and cell surface proteins that is involved in numerous function in inflammation and immunity
Primary humoral defense system against bacterial and viral infections
heat labile (can be destroyed by heating serum)
most of the complement proteins are produced by the liver hepatocytes
C3 is the most [...]
Intro
all blood cells and Lymphocytes come from pluripotent stem cells in the bone marrow
We can distinguish stem cells from other bone marrow components
Developmental Pathway
Platelets, Erythrocytes, Eosinophils, Neutrophils, Basophils, Monocytes, Macrophages
Myeloid Stem Cell
Bone Marrow Pluripotential Stem Cell
Lymphoid Stem Cell
¯
T Cell Precursor B Cell Precursor
¯ ¯
Thymus Mature B Cells (B cell areas)
¯
Mature T [...]
Ø CMI- immune reactions in which T cells play a central role as effector cells instead of regulatory cells
includes T-cell cytotoxicity and Delayed type Hypersensitivity
Granulomatous responses usually result from DTH reactions to poorly degradable antigens, although Ab responses can [...]
Definition: An endogenous immune response (autoantibody and/or autoreactive T cell) to an endogenous antigen
Normal Occurences
Probably occur all of the time to help clear defective or denatured molecules
These are rapidly cleared by the RE system
Abnormal Occurences
when large amounts or autoantibodies or autoreactive T cells are produced which damage host tissue, an autoimmune [...]
once Ab have been made they can be used for a variety of diagnostic assays in the lab to detect the presence or absence of a particular antigen or bacterium or virus in a sample
For example, the use of Ab specific for the myriad of RBC antigens has made routine transfusion possible [...]
Ø Antibody (Humoral) mediated immunity- extracellular bacteria or bacterial products
Ø Cell Mediated Immunity (CMI)- primarily operates against intracellular viral, bacterial, as well as fungal antigens
Ø “DOUBLE-EDGE SWORD”- in most cases your immune system is protective, but it can also be destructive.
Ø Immunopathology- tissue damage resulting from the immune response
allergies, [...]
Remember innate vs. adaptive
Remember anitgens have certain properties that allow them to be immunogenic. Such as: size, foreigness, polysaccharides
Cytokines
Properties
MODULATE IMMUNE/ INFLAMMATORY RESPONSES (allow for balance)
inc. small peptides and glycoproteins
Made by variety of cell types including
accessory cells
leukocytes
somatic cells
short ½ life; one cell can make many different [...]
Structural Features of IgG
2 L-chain domains; 4 H-chain domains
Inter and intrachain disulfide bonds hold IgG together
Single carbohydrate moiety in CH2 domain (plays role in transport/secretion)
Biologic Properties of IgG (8)
1. Agglutination & Precipitate Formation
2. Placental Passage: selectively passed through placenta [...]
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